Epigenetic alterations and microbiota changes in the saliva of individuals with binge-eating spectrum disorders compared with normal weight healthy controls

Aims: Binge-eating spectrum disorders, including bulimia nervosa (BN) and binge-eating disorder (BED), have psychological, behavioral, and physical effects, which present significant challenges for accurate diagnosis and treatment. Identifying biomarkers is thus of relevance to improve diagnostic and treatment strategies. Main methods: Saliva collected from female individuals with BED (n = 20), BN (n = 17), and normal weight healthy controls (NW-HC) (n = 20) was analyzed to assess salivary microbiome, exosomal miRNA expression, and DNA methylation of dopaminergic system gene components. Key findings: Microbial diversity was significantly reduced in BED and BN groups compared to NW-HC. Differential abundance analysis revealed that Bacilli (class-level) were enriched in BN and BED, while Lachnospirales (order-level) were significantly depleted in BN compared to NW-HC. In total, 79 miRNAs were differentially expressed in patients compared with controls. Alteration in four of these miRNAs (let-7b-5p, mir-15b-5p, mir-429, and mir-221-3p) identified via network analysis as potentially relevant to psychiatric disorders, were confirmed to be significantly upregulated in both BED and BN compared with controls. Significant hypomethylation at specific CpG sites of the DAT1 gene was also observed in BED and BN groups relative to controls. Correlation analysis highlighted significant associations between specific microbiota genera, miRNA expression, and DNA methylation of DAT1 in both the BED and BN groups. Significance: Our findings provide new evidence on the role of epigenetic modifications linked to alterations in salivary microbial composition and diversity in BED and BN, opening new avenues for future research and therapeutic interventions in eating disorders targeting miRNAs and microbiota.